Absence of imprinting of HLA class Ia genes leads to co-expression of biparental alleles on term human trophoblast cells upon IFN-gamma induction.
Human trophoblast cells have developed various efficient regulatory mechanisms to prevent cell surface expression of the classical HLA-A, -B, and (but not always) -C class I molecules. This allows them to escape maternal alloimmune attack during pregnancy. However, recent results have demonstrated that such a lack of expression could be reversed in villous cytotrophoblast cells purified from term placenta by in vitro IFN-gamma treatment. In this context, we investigated whether both maternal and paternal HLA class Ia antigens were co-dominantly expressed in such trophoblast cells. Using polymerase chain reaction sequence-specific primers for HLA-A and HLA-C alleles, we detected transcripts of both paternal and maternal origins, showing that these genes were not affected by genomic imprinting, at least in term placenta. After in vitro IFN-gamma treatment, the polymorphic HLA-A and HLA-B antigens of both parental origins become detectable at the cell surface, as assessed by flow cytometry and/or complement-dependent microtoxicity test. Appearance of paternal antigens on trophoblast cells upon IFN-gamma induction raises the question of the in vivo biological consequences of this phenomena, in term of materno-fetal tolerance and in particular of a potential allogeneic cytotoxic immune response.
Lenfant
F
F
Institut National de la Santé et de la Recherche Médicale U.395, CHU Purpan, Toulouse, France.
Fort
M
M
Rodriguez
A M
AM
Campan
A
A
Aguerre-Girr
M
M
Sommer
E
E
Abbal
M
M
Ohayon
E
E
Le Bouteiller
P
P
D000483:Alleles; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000276:immunology*; D005799:Genes, Dominant / Q000276:immunology; D005805:Genes, MHC Class I; D018392:Genomic Imprinting / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000235:genetics; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D008297:Male; D011247:Pregnancy; D014158:Transcription, Genetic / Q000276:immunology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D007371:Interferon-gamma